The effects of PVP(Fe(III)) catalyst on polymer molecular weight and gene delivery via biodegradable cross-linked polyethylenimine

Victor W.T. Shum, Nathan P. Gabrielson, M. Laird Forrest, Daniel W. Pack

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Crosslinked, degradable derivatives of low-molecular-weight polyethylenimine (PEI) are relatively efficient and non-cytotoxic gene delivery agents. To further investigate these promising materials, a new synthetic approach was developed using a poly(4-vinylpyridine)-supported Fe(III) catalyst (PVP(Fe(III))) that provides more facile synthesis and enhanced control of polymer molecular weight. Methods: Biodegradable polymers (D.PEI) comprising 800-Da PEI crosslinked with 1,6-hexanediol diacrylate and exhibiting molecular weights of 1.2, 6.2, and 48 kDa were synthesized utilizing the PVP(Fe(III)) catalyst. D.PEI/DNA polyplexes were characterized using gel retardation, ethidium bromide exclusion, heparan sulfate displacement, and dynamic light scattering. In vitro transfection, cellular uptake, and cytotoxicity of the polyplexes were tested in human cervical cancer cells (HeLa) and human breast cancer cells (MDA-MB-231). Results: D.PEIs tightly complexed plasmid DNA and formed 320- to 440-nm diameter polyplexes, similar to those comprising non-degradable, 25-kDa, branched PEI. D.PEI polyplexes mediated 2- to 5-fold increased gene delivery efficacy compared to 25-kDa PEI and exhibited 20% lower cytotoxicity in HeLa and no toxicity in MDA-MB-231. In addition, 2- to 7-fold improved cellular uptake of DNA was achieved with D.PEI polyplexes. Conclusions: PVP(Fe(III)) catalyst provided a more controlled synthesis of D.PEIs, and these materials demonstrated improved in vitro transfection efficacy and reduced cytotoxicity.

Original languageEnglish (US)
Pages (from-to)500-510
Number of pages11
JournalPharmaceutical Research
Volume29
Issue number2
DOIs
StatePublished - Feb 2012

Keywords

  • Biodegradable polymer
  • Non-viral gene delivery
  • Polyethylenimine
  • Polymer supported ferric chloride

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'The effects of PVP(Fe(III)) catalyst on polymer molecular weight and gene delivery via biodegradable cross-linked polyethylenimine'. Together they form a unique fingerprint.

Cite this